tbuckley/cabot-search huggingface dataset:
AB0066 EFFECT AND MECHANISM OF QINXITONG ON BIOLOGICAL BEHAVIOR OF SYNOVIAL FIBROBLASTS IN RHEUMATOID ARTHRITIS
Authors: Y. Lv, J. Zhang, Y. Liu
Journal: Annals of the Rheumatic Diseases (2022)

Background Chinese medicine has been used widely for the treatment of RA for a long history in China. The Fifth Hospital of Xi’an has treated patients of RA with QinXiTong(QXT) for 40 years which is mainly based on the water extract from Caulis Sinomenii(CS). However, the molecular mechanism of its anti-rheumatism effect remains unclear. Objectives To investigate the effects of Qinxitong on proliferation, apoptosis, migration and invasion of synovial fibroblasts in rheumatoid arthritis and its mechanism. Methods Taking rheumatoid arthritis synovial fibroblast cell line MH7A as the research object. The cells were divided into four groups according to the different dosage of Qinxitong intervention, namely control group, low dose group (QXT-20), medium dose group (QXT-50) and high dose group (QXT-100). CCK-8 assay was used to detect cell proliferation, flow cytometry was used to detect cell apoptosis, Transwell assay was used to detect cell migration and invasion, and Western blotting was used to detect total Erk protein (t-Erk) and phosphorylated Erk protein (p-Erk) expression levels. Results CCK-8 assay showed that Qinxitong could inhibit the proliferation of MH7A cells, compared with the control group, cell proliferation in QXT-50 and QXT-100 groups was significantly reduced ( p&lt; 0.05) after 24h, 48, and 72h intervention, the effect of QXT-100 was even more significant ( p&lt; 0.001); flow cytometry showed that QXT could promote apoptosis of MH7A cells, compared with the control group, the apoptosis rate of QXT-50 and QXT-100 groups was significantly increased ( p&lt; 0.05); Transwell assay showed that QXT could inhibit the migration and invasion of MH7A cells, compared with the control group, the QXT-50 and QXT-100 groups showed significantly higher inhibition of migration and invasion of MH7A cells ( p&lt; 0.05); Western blotting showed that QXT could reduced p-Erk expression level, compared with the control group, the decrease of p-Erk expression level in QXT-50 and QXT-100 groups was statistically significant ( p&lt; 0.001). Conclusion Qinxitong can inhibit the proliferation, promote apoptosis, inhibit migration and invasion of rheumatoid arthritis synovial fibroblasts by regulating Erk signaling pathway, providing scientific basis for clinical application of Qixintong. Disclosure of Interests None declared
POS0437 CIRC_ 0003972 STUDY ON FIBROBLAST LIKE SYNOVIAL CELLS IN RHEUMATOID ARTHRITIS THROUGH IMMUNE REGULATION
Authors: P. Liu, T. Zhang, Y. Yu
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is a common chronic autoimmune disease involving multiple joint symmetry. The main pathological changes are fibroblast like synovial (FLS) cell proliferation and bone destruction. Circular RNA (circrna) is a special type of noncoding RNA formed by reverse splicing of linear RNA, which has high stability in organisms. Research shows that circ_ 0003972 is a circrna found to be significantly up-regulated in RA patients in recent years, and its level is significantly positively correlated with DAS28 score and patients with joint tenderness (Wen et al, 2020b)[1]. However, The role of CIRC_0003972 in the pathological progression of RA synovium has not been confirmed. Our research aims to reveal Role of Circ_0003972. Objectives Circular RNAs (circrnas) have been shown to play an important role in the progression of RA. The purpose of this study is to explore Circ_ 0003972 Role and mechanism of in the progression of RA. Methods The gene expression was determined by real-time quantitative PCR. The proliferation and apoptosis of human RA fibroblast like synovial (fls-ra) cells were measured by cell counting kit 8, edu staining and flow cytometry. Western blot analysis was performed to measure protein expression, and ELISA was used to check the concentration of inflammatory factors. Double luciferase reporter gene detection and rip detection confirmed mir-654-5p and Interaction between Circ_0003972. Results Circ_0003972 is expressed in RA patients and fls-ra cells. Circ_ 0003972 knockdown inhibits proliferation and inflammation and promotes TNF-α Flra-induced apoptosis. Mir-654-5p is down regulated in RA patients and fls-RA cells, and it can be expressed by Circ_ 0003972 absorption. Mir-654-5p inhibitor reversed Circ_0003972 silencing on TNF-α Effects of induced hfls-RA on cell proliferation, inflammation and apoptosis. Conclusion Circ_0003972 may promote the proliferation and inflammation of FLS-RA cells and accelerate the pathological progress of RA by regulating mir-654-5p. References [1]Wen J, Liu J, Zhang P, et al. RNA-seq reveals the circular RNA and miRNA expression profile of peripheral blood mononuclear cells in patients with rheumatoid arthritis[J]. Bioscience Reports, 2020, 40(4). Disclosure of Interests None declared.
AB1492 COMPARISON OF TELEREHABILITATION METHODS FOR SYSTEMIC SCLEROSIS PATIENTS IN THE COVID-19 ERA: A RANDOMIZED CONTROLLED STUDY
Authors: T. Civi Karaaslan, E. Tarakci, O. Keles, Y. Aslan Keles, S. Ugurlu
Journal: Annals of the Rheumatic Diseases (2022)

Background Scleroderma (SSc) is an autoimmune connective tissue disease progressing with fibrosis. SSc patients need to be protected from epidemic diseases as well as rehabilitation needs. For this reason, it is important for them to continue their exercises in an environment where they can be both rehabilitated and protected from infectious diseases. Objectives In this study, it was aimed to reveal the effects of exercises performed by telerehabilitation on individuals with Scleroderma with hand involvement and to compare the effects of real-time telerehabilitation (RTT) and asynchronous telerehabilitation (AT). Methods Forty-two participants with a mean age of 44.17±11.05 years were included in the study. The patients were divided into three groups and followed for 8 weeks. RTT was applied to the 1st group and AT was applied to the 2nd group, and the 3rd group was the control group. Participants’ finger and wrist joint range of motion (ROM) were evaluated with a goniometer, upper extremity functions were evaluated with Scleroderma Hand Mobility Test (HAMIS), Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and 9Hole Peg Test (9HPT), grip strength was evaluated with a dynamometer, superficial sense of touch was evaluated with the Semmes Weinstein Monofilament test, activities of daily living (ADL) were evaluated with the Michigan Hand Outcomes Questionnaire (MHQ), and general health status was evaluated with the Scleroderma Health Assessment Questionnaire (SHAQ). Results There were improvements in finger and wrist ROM, upper extremity functions and ADL parameters in the RTT group; and there were improvement in finger ROM and hand functions in the AT group (p&lt;0.05). Wrist radial deviation ROM decreased in the control group (p&lt;0.05). Significant differences were noted between the groups in finger ROM and upper extremity functions after treatment (p&lt;0.05). Conclusion Our study shows that exercises performed via RTT and AT are effective in individuals with Scleroderma with hand involvement, and RTT has additional benefits. References [1]Sendur N, Sendur UG. Scleroderma. Turkiye Klinikleri J Dermatol. 2018;15-20. [2]Baron M, Lee P, Keystone EC. The articular manifestations of progressive systemic sclerosis (scleroderma). Ann Rheum Dis. 1982;41(2):147-152. [3]Spinella A, Magnani L, De Pinto M, et al. Management of Systemic Sclerosis Patients in the COVID-19 Era: The Experience of an Expert Specialist Reference Center. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 2021; 15:1–3. [4]Smith AC, Thomas E, Snoswell CL, et al. Telehealth for global emergencies: Implications for coronavirus disease 2019 (COVID-19). J Telemed Telecare 2020;26(5):309-313. Disclosure of Interests None declared
AB0311 RHEUMATOID ARTHRITIS AND OSTEOPOROSIS: FREQUENCY AND ASSOCIATED FACTORS
Authors: M. Brahem, R. Sarraj, A. Ben Salem, R. Grassa, S. Abdellatif, H. Hachfi, Y. Mohamed
Journal: Annals of the Rheumatic Diseases (2022)

Background In rheumatoid arthritis (RA), persistent systemic inflammation may cause bone and cartilage destruction and systemic osteoporosis (OP). Objectives We conducted this study to determine the frequency of OP in RA patients and to focus on associated factors. Methods This is a retrospective descriptive and analytic study including consecutive RA patients. The epidemiological, clinical, biological data and the measurement of bone mineral density were collected from patients’ records. A statistical analysis was performed to study the clinico-biological profile of osteoporotic patients and determine factors associated with the development of OP in RA patients. Results Seventy-one of RA patients were recruited: 67 females (94.4%) and 4 males (5.6%) with a mean age of 54.28 years ± 11.09 [30-75]. OP was noted in 45.1% of cases (32 patients). The mean T-scores at the lumbar and femoral sites were -2.7 ± 0.6 SD and -1.3 ± 1 SD, respectively. Patients with OP were older (58.8 ± 7.6 years vs 50.5 ± 12.1 years; p &lt;0.01) and with a greater number of postmenopausal women than patients with normal bone density (68.7% vs 41%; p=0.02). Osteoporotic patients had RA duration longer than the other group (15.2 ± 12.5 years vs 11.9 ± 8.2 years; p=0.02) and more extra-articular manifestations associated with RA (100% vs 76.9%; p &lt; 0.01). Both groups were treated with corticosteroid drugs with similar frequency, although patients with normal bone density received biotherapy more frequently than patients with OP (23% vs 18.7%; p= 0.03). The two groups had almost similar disease activity DAS28 ESR (44,3 ± 34 vs 42.7 ± 30.7; p=0.2). The following parameters were not associated with the occurrence of OP in our series: gender, smoking, BMI, ESR, CRP, ACPA, RF, erosive and deforming character of RA. Conclusion OP is an extra-articular disease that must be systematically screened throughout the follow-up. In our study, there was no significant difference in disease activity at both groups of patients. However, patients with OP had longer duration of RA, more extra-articular manifestations and were less frequently treated with biotherapy. References [1]Hauser B, Riches PL, Wilson JF, Horne AE, Ralston SH. Prevalence and clinical prediction of osteoporosis in a contemporary cohort of patients with rheumatoid arthritis. Rheumatology (Oxford). 2014 Oct;53(10):1759-66. Disclosure of Interests None declared
Whole-genome CRISPR screening identifies <i>N-</i>glycosylation as a genetic and therapeutic vulnerability in <i>CALR</i>-mutant MPNs
Authors: Jonas S. Jutzi, Anna E. Marneth, Michele Ciboddo, Angel Guerra-Moreno, María José Jiménez-Santos, Anastasia Kosmidou, James W. Dressman, Hongyan Liang, Rebecca Hamel, Patricia Lozano, Elisa Rumi, John G. Doench, Jason Gotlib, Anandi Krishnan, Shannon Elf, Fátima Al-Shahrour, Ann Mullally
Journal: Blood (2022)

Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR mutations cause MPNs has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies in CALR-mutant MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen in mutant CALR-transformed hematopoietic cells. We found that genes in the N-glycosylation pathway (among others) were differentially depleted in mutant CALR-transformed cells as compared with control cells. Using a focused pharmacological in vitro screen targeting unique vulnerabilities uncovered in the CRISPR screen, we found that chemical inhibition of N-glycosylation impaired the growth of mutant CALR-transformed cells, through a reduction in MPL cell surface expression. We treated Calr-mutant knockin mice with the N-glycosylation inhibitor 2-deoxy-glucose (2-DG) and found a preferential sensitivity of Calr-mutant cells to 2-DG as compared with wild-type cells and normalization of key MPNs disease features. To validate our findings in primary human cells, we performed megakaryocyte colony-forming unit (CFU-MK) assays. We found that N-glycosylation inhibition significantly reduced CFU-MK formation in patient-derived CALR-mutant bone marrow as compared with bone marrow derived from healthy donors. In aggregate, our findings advance the development of clonally selective treatments for CALR-mutant MPNs.
AB1165 THE ROLE OF MOLECULAR MIMICRY IN SARS-CoV-2 RELATED AUTOIMMUNE RHEUMATIC DISEASES
Authors: C. Liaskos, E. Patrikiou, L. Komorowski, C. Tsigalou, A. Tsirogianni, L. Sakkas, D. Bogdanos
Journal: Annals of the Rheumatic Diseases (2022)

Background Several studies suggested that SARS-CoV-2 infection may induce autoantibodies related to autoimmune rheumatic diseases (ARD). Objectives To determine whether polyclonal antibodies from SARS-CoV-2 uninfected patients with ARDs cross-react with SARS-CoV-2 and vice versa. Methods 90 sera positive at high-titres for 23 common autoantibodies (all sera stored before 2018), were tested for reactivity against proteins of SARS-CoV-2 (spike protein S1, nucleocapsid NC etc) by ELISA and CMIA. Vice versa, 10 monoclonal antibodies against S1 protein (most of them against RBD) were tested for autoantibody reactivity by indirect immunofluorescence, ELISA, immunoblot and dot/line immunoassays coated with different antigens. Ten post-COVID sera with high titers of anti-Spike abs were tested by ELISAs for reactivity against various autoantigens related to ARDs. Results 88 out of 90 samples (%), were totally unreactive to SARS-CoV-2 proteins; 2 sera, one anti-CCP and one anti-CENP reacted against S protein. All sera tested negative for neutralized abs against SARS-CoV-2. None of 10 sera from SARS-CoV-2 infected patients reacted with different autoantigens by molecular assays. None of the 10 monoclonal abs against S1 protein reacted with 23 different self-antigens. On HEp2 cells as substrate for IIF, 3 of the 10 monoclonal abs gave a low-titre coarse speckled pattern. No reactivity was found by IIFL using tissue substrates. Conclusion Our data do not suggest a dominant role for molecular mimicry and immunological cross reactivity as a trigger of autoantibodies related to ARDs. Disclosure of Interests Christos Liaskos: None declared, Eleni Patrikiou: None declared, Lars Komorowski Employee of: emploee of EUROIMMUN Medizinische Labordiagnostika, Christina Tsigalou: None declared, Alexandra Tsirogianni: None declared, Lazaros Sakkas: None declared, Dimitrios Bogdanos: None declared
AB0404 DEPENDENCE OF COMPLICATIONS IN TOTAL HIP AND KNEE ARTHROPLASTY ON THE TREATMENT OF RHEUMATOID ARTHRITIS.
Authors: A. Khramov, M. Makarov, S. Makarov, V. Amirdzhanova, S. Maglevaniy, I. Kushnareva, T. C. Phan
Journal: Annals of the Rheumatic Diseases (2022)

Background Surgical treatment of patients with rheumatoid arthritis (RA) is associated with an increased risk of complications. This is due to the presence of an inflammatory process, a variety of variants of the course of the disease, reduced physical activity, the severity of functional disorders, prolonged therapy with glucocorticoids, disease-modifying and genetically engineered biological drugs, osteoporosis, as well as the activity of the underlying disease. Objectives to conduct a comparative analysis of the effect of RA treatment on local complications, such as periprosthetic infection, periprosthetic fractures, wound complications, ligamentous disorders in hip and knee total arthroplasty in patients with RA. Methods 1113 arthroplasties of large joints in patients with RA, which were performed in the period from 2002 to 2020, were analyzed. Of these, 649 total knee replacements (TKA) and 464 total hip replacements (THA) were performed. Results In patients with therapy of methotrexate at an average dose of 12.5 mg per week, the incidence of local complications was 7.87%. In patients receiving Leflunomide (Arava), complications were detected in 9.29% of cases. In group of patients with Sulfasalazine (SSZ) intake, local complications were detected in 7.73% of cases. The complication rate of 7.01% was determined in group of patients who received Glucocorticoids (GC) at an average dose of 7.5 mg (recalculation in Prednisone). 1.87% of complications were observed in patients with intake of genetically engineered biological drugs (bDMARD). The highest incidence of local complications was found in patients with RA who had no therapy (27.27%). Statistical data analysis revealed a significantly higher number of complications in the group of RA patients (p&lt;0.005). Analyzing each type of complications, significant differences were also obtained (p&lt;0.005). Conclusion The risk of local complications was 3 or more times higher in group of patients with RA without any treatment. So, arthroplasties of large joints in patients with RA without treatment are often accompanied by a high risk of intra- and postoperative complications. Disclosure of Interests None declared
AB1003 EFFECTIVENESS OF CLASSIC VERSUS AQUATIC REHABILITATION IN GONARTHROSIS: LEQUESNE SCORE
Authors: R. Maaoui, K. Ben Amor, M. Hfaidh, N. Mouhli, H. Rahali, I. Ksibi, M. Slouma, L. Ben Ammar, L. Metoui, R. Dhahri, I. Gharsallah
Journal: Annals of the Rheumatic Diseases (2022)

Background Gonarthrosis is a benign knee condition, but it can become disabling if poorly managed. The evaluation of the functional impact of gonarthrosis is based on Lequesne’s algofunctional index [1], thus judging the effectiveness or failure of the proposed treatment. Water gymnastics is increasingly prescribed in the management of this pathology. Objectives The main aim of our work was to compare the efficacy of aquatic gymnastics with conventional rehabilitation in patients with gonarthrosis using Lequesne’s algofunctional index. Methods This is a prospective, comparative study conducted over a period of 15 months, between September 2016 december 2017, including 120 patients recruited at the outpatient clinic of the Physical Medicine and Functional Rehabilitation Department of The HMPIT, in whom the diagnosis of gonarthrosis was made according to the ACR criteria. The patients were randomly divided into 2 groups of 60 patients each. The first group, called G1, received a conventional rehabilitation program. The second group, called G2, received water gymnastics. Two evaluations were made, the first (T1) before the beginning of the rehabilitation and the second (T2) at the end of the eight weeks of treatment. Results The mean age of the general population was 54.85 ± 9.501 years [40- 81 years]. The mean age of G1 was 59.07 ± 10.275 years versus 50.63 ± 6.425 years for G2. Thus, there was a female predominance with a sex ratio M/F of 0.11 in G1 and 0.57 in G2. Lequesne’s algofunctional index was initially 11.46 ± 3.2 in G1 patients and 8.7 ± 1 in G2 patients with a statistically significant difference between the 2 groups (p&lt;0.001). The discomfort according to the Lequesne algofunctional index was very important and unbearable in 69% of the cases in G1 against 41% of the cases in G2. The Lequesne index was ≥ 10 in 46 patients in G1 (i.e. 77%) versus 32 patients in G2 (i.e. 53%). After conventional rehabilitation, there was a 10% improvement in this index compared with a 28% improvement after water gymnastics with a statistically significant difference between the 2 groups (p&lt;0.001). Conclusion The effectiveness of functional treatment whether aquatic or classic was well demonstrated by Lequesne’s algofunctional index, with better result for aquatic rehabilitation. The best would be to combine the two according to the initial functional capacities of the patient to ensure his adherence to the rehabilitation program. References [1]Guermazi M, Mezganni M, Yahia M, Poiraudeau S, Fermanian J, Elleuch MH, et al. Translation and construct validity of the Lequesne index for Arab speaking North African patients with osteoarthritis of the knee. Ann Readapt Med Phys. 2004;47(5):195-203. Disclosure of Interests None declared
POS0860 ULTRA-HIGH FREQUENCY ULTRASOUND FOR DIGITAL ARTERIES: COMPLETING THE CHARACTERIZATION OF VASCULOPATHY IN SYSTEMIC SCLEROSIS
Authors: M. DI Battista, S. Vitali, S. Barsotti, R. Morganti, V. Dini, M. Romanelli, A. Della Rossa, M. Mosca
Journal: Annals of the Rheumatic Diseases (2022)

Background Despite microangiopathy is the hallmark of systemic sclerosis (SSc), macrovascular involvement is arousing interest. In particular, proper palmar digital arteries (PPDA) play an important role in Raynaud’s phenomenon and can contribute to the exacerbation of vascular damage. However, PPDA full characterization is still an unmet need. Objectives To assess the state of PPDA in a cohort of patients with SSc using ultra-high frequency ultrasound (UHFUS), comparing the results with those obtained in healthy controls (HC) and looking for any association with SSc-specific characteristics. Correlations between UHFUS features of PPDA and microvascular bed were also investigated. Methods Consecutive SSc patients without active digital ulcers and HC were enrolled. Epidemiological and SSc-specific data were collected. Each subject underwent UHFUS (70 MHz) evaluation of PPDA (2 per finger, from II to V finger bilaterally), searching for occluded or not viewable vessels and measuring the thickness of the three arterial layers, as well as the systo-diastolic excursion range. Finally, microvascular bed was investigated by capillaroscopy and laser speckle contrast analysis (LASCA). Results Forty-six SSc patients (87% female, mean age 55.5 years, mean disease duration 8.2 years) and 15 HC matched for age and sex were enrolled. UHFUS in SSc revealed 123 (16.7%) PPDA occluded or not viewable, whereas in HC they were all patent. Considering the finger with at least one of the two PPDA occluded or not viewable as ultrasonographically pathological, 30 (65.2%) patients presented at least one pathological finger (Figure 1). All three arterial layers were significantly thicker in SSc than in HC (p&lt;0.001 for all), as well as systo-diastolic excursion range was significantly reduced in SSc (p&lt;0.001). On 63 fingers previously affected by digital ulcers, 73% were ultrasonographically pathological. A direct correlation emerged between disease duration and the thickness of all three arterial layers (intima p&lt;0.001; ρ=0.527; intima-media p&lt;0.001; ρ=0.502; intima-media-adventitia p=0.001; ρ=0.491). No significant correlations emerged between capillaroscopy or LASCA findings and UHFUS features. Figure 1. Representation of the number of ultrasonographically pathological fingers per patient. Conclusion SSc presents a vasculopathic involvement of PPDA well characterized by UHFUS, a useful diagnostic tool able to show also subclinical vascular impairment. The lack of correlations between UHFUS and capillaroscopy or LASCA reflects the existence of vasculopathic processes that are not exactly the same. Thus, UHFUS evaluation of PPDA emerges as complementary to microcirculation assessment, in order to obtain a more accurate and complete characterization of the vasculopathy in SSc. Disclosure of Interests None declared